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Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization
Ainiwaer, Aizier1; Qian, Zhenwei2; Wang, Jianxun3; Zhao, Qi4; Lu, Yinying1,2
2024-11-22
Source PublicationDiscover Oncology
ISSN2730-6011
Volume15Issue:1Pages:696
Abstract

The liver is the predominant metastatic site for diverse cancers, including pancreatic and colorectal cancers (CRC), etc. The high incidence of hepatic metastasis of pancreatic cancer is an important reason for its refractory and high mortality. Therefore, it is important to understand how metastatic pancreatic cancer affects the hepatic tumor immune microenvironment (TME) in patients. Here, we characterized the TME of liver metastases unique to pancreatic cancer by comparing them with CRC liver metastases. We integrated two single-cell RNA-seq (scRNA-seq) datasets including tumor samples of pancreatic cancer liver metastasis (P-LM), colorectal cancer liver metastasis (C-LM), primary pancreatic cancer (PP), primary colorectal cancer (PC), as well as samples of peripheral blood mono-nuclear cells (PBMC), adjacent normal pancreatic tissues (NPT), to better characterize the heterogeneities of the microenvironment of two kinds of liver metastases. We next performed comparative analysis on cellular compositions between P-LM and C-LM, found that Mph_SPP1, a subset of macrophages associated with angiogenesis and tumor invasion, was more enriched in the P-LM group, indicating this kind of macrophages provide a TME niche more vulnerable for pancreatic cancers. Analysis of the developmental trajectory implied that Mph_SPP1 may progressively be furnished with increased expression of genes regulating endothelium. Cell–cell communications analysis revealed that Mph_SPP1 potentially interacts with endothelial cells in P-LM via FN1/SPP1-ITGAV/ITGB1, implying this macrophage subset may construct an immunosuppressive TME for pancreatic cancer by regulating endothelial cells. We also found that Mph_SPP1 has a prognostic value in pancreatic adenocarcinoma that is not present in colon adenocarcinoma or rectum adenocarcinoma. This study provides a new perspective for understanding the characteristics of the hepatic TME in patients with liver metastatic cancer. And it provides a subset of macrophages specifically associated with the liver metastasis of pancreatic cancer, and its detection and intervention have potential value for preventing the metastasis of pancreatic cancer to the liver.

KeywordLiver Metastasis Scrna-seq Pancreatic Cancer Colorectal Cancer Spp1
DOI10.1007/s12672-024-01566-0
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaOncology ; Endocrinology & Metabolism
WOS SubjectOncology ; Endocrinology & Metabolism
WOS IDWOS:001362455600002
PublisherSPRINGER, ONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES
Scopus ID2-s2.0-85210101186
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorZhao, Qi; Lu, Yinying
Affiliation1.Comprehensive Liver Cancer Center, The 5Th Medical Center of the PLA General Hospital, Beijing, China
2.Peking University 302 Clinical Medical School, Beijing, 100039, China
3.Shenzhen Cell Valley Biopharmaceuticals Co., LTD, Shenzhen, 518118, China
4.MoE Frontiers Science Center for Precision Oncology, Faculty of Health Sciences, University of Macau, Taipa, SAR, Macao
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Ainiwaer, Aizier,Qian, Zhenwei,Wang, Jianxun,et al. Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization[J]. Discover Oncology, 2024, 15(1), 696.
APA Ainiwaer, Aizier., Qian, Zhenwei., Wang, Jianxun., Zhao, Qi., & Lu, Yinying (2024). Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization. Discover Oncology, 15(1), 696.
MLA Ainiwaer, Aizier,et al."Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization".Discover Oncology 15.1(2024):696.
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